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1.  Association between Peripheral Oxidative Stress and White Matter Damage in Acute Traumatic Brain Injury 
BioMed Research International  2014;2014:340936.
The oxidative stress is believed to be one of the mechanisms involved in the neuronal damage after acute traumatic brain injury (TBI). However, the disease severity correlation between oxidative stress biomarker level and deep brain microstructural changes in acute TBI remains unknown. In present study, twenty-four patients with acute TBI and 24 healthy volunteers underwent DTI. The peripheral blood oxidative biomarkers, like serum thiol and thiobarbituric acid-reactive substances (TBARS) concentrations, were also obtained. The DTI metrics of the deep brain regions, as well as the fractional anisotropy (FA) and apparent diffusion coefficient, were measured and correlated with disease severity, serum thiol, and TBARS levels. We found that patients with TBI displayed lower FAs in deep brain regions with abundant WMs and further correlated with increased serum TBARS level. Our study has shown a level of anatomic detail to the relationship between white matter (WM) damage and increased systemic oxidative stress in TBI which suggests common inflammatory processes that covary in both the peripheral and central reactions after TBI.
doi:10.1155/2014/340936
PMCID: PMC3996315  PMID: 24804213
2.  Peripheral Leukocyte Apoptosis in Patients with Parkinsonism: Correlation with Clinical Characteristics and Neuroimaging Findings 
BioMed Research International  2014;2014:635923.
Apoptosis of both brain neurons and peripheral blood leukocyte is believed to be an important biomarker for evaluating the functional status of Parkinson's disease (PD). However, their correlation remains unknown. A better understanding of the pathophysiology of neurodegeneration is essential for the treatment and prevention of PD. The present study demonstrated that leukocyte apoptosis is significantly higher in PD patients and is associated with central dopamine neuron loss by using 99mTc-TRODAT-1 SPECT. The leukocyte apoptosis and striatal dopamine transporter uptake ratios were further associated with increased severity and longer duration of disease. The interaction between brain and systemic inflammation may be responsible for the neurodegenerative disease progression.
doi:10.1155/2014/635923
PMCID: PMC3984850  PMID: 24795890
3.  Investigation of the caspase-dependent mitochondrial apoptotic pathway in mononuclear cells of patients with systemic lupus erythematosus 
Background
This study aimed to explore the role of apoptosis initiators, caspase-9, caspase-10, mitochondrial anti-viral signaling protein (MAVS), and interferon regulatory factor 7 (pIRF7), in patients with systemic lupus erythematosus (SLE).
Methods
Leukocyte apoptosis was determined by flow cytometry, including annexin V, APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 35 patients with SLE, 15 disease controls, and 17 volunteer normal controls. Levels of caspase-9, caspase-10, MAVS, and pIRF7 in mononuclear cells and the disease activity index (SLEDAI) in the SLE patients were determined. Correlation among intracellular adaptor proteins and caspase levels were calculated.
Results
The SLE patients had higher APO2.7 in total leukocyte, lymphocyte, and monocytes, and higher late apoptosis markers in total leukocytes and neutrophils than normal controls (all p < 0.05). Disease activity was positively associated with the APO2.7 of CD19+ cells in SLE, but negatively associated with MAVS and caspase-9 levels (all p < 0.05). Markers of viral infection and anti-virus transcription factors like MDA5, MAVS, and pIRF7 were significantly higher in SLE patients than in disease controls (p < 0.05). Caspase-9 and caspase-10 levels positively correlated with MAVS and pIRF7 in SLE patients (p < 0.05).
Conclusions
The disease activity of SLE is positively associated with APO2.7 level of CD19+ cells but negatively associated with MAVS and caspase-9 levels, which all point to a mitochondrial pathway.
doi:10.1186/s12967-014-0303-1
PMCID: PMC4226892  PMID: 25370148
Caspase; Leukocyte apoptosis; Systemic lupus erythematosus; Interferon
4.  The Feasibility of Using CT-Guided ROI for Semiquantifying Striatal Dopamine Transporter Availability in a Hybrid SPECT/CT System 
The Scientific World Journal  2014;2014:879497.
A hybrid SPECT/CT system provides accurate coregistration of functional and morphological images. CT-guided region of interest (ROI) for semiquantifying striatal dopamine transporter (DAT) availability may be a feasible method. We therefore assessed the intra- and interobserver reproducibility of manual SPECT and CT-guided ROI methods and compared their semiquantitative data with data from MRI-guided ROIs. We enrolled twenty-eight patients who underwent Tc-99m TRODAT-1 brain SPECT/CT and brain MRI. ROIs of the striatal, caudate, putamen, and occipital cortex were manually delineated on the SPECT, CT, and MRI. ROIs from CT and MRI were transferred to the coregistered SPECT for semiquantification. The striatal, caudate, and putamen nondisplaceable binding potential (BPND) were calculated. Using CT-guided ROIs had higher intra- and interobserver concordance correlation coefficients, closer Bland-Altman biases to zero, and narrower limits of agreement than using manual SPECT ROIs. The correlation coefficients of striatal, caudate, and putamen BPND were good between manual SPECT and MRI-guided ROI methods and even better between CT-guided and MRI-guided ROI methods. Conclusively, CT-guided ROI delineation for semiquantifying striatal DAT availability in a hybrid SPECT/CT system is highly reproducible, and the semiquantitative data correlate well with data from MRI-guided ROIs.
doi:10.1155/2014/879497
PMCID: PMC4233671  PMID: 25531005
5.  Predictors and long-term outcome of seizures in human immuno-deficiency virus (HIV)-negative cryptococcal meningitis 
BMC Neurology  2014;14(1):208.
Background
Seizures are one of the most important neurologic complications of human immuno-deficiency virus (HIV)-negative cryptococcal meningitis. A better understanding of the risk associated factors can help predict those who will require treatment.
Methods
This 22-year retrospective study enrolled 180 patients. Prognostic variables independently associated with seizures or fatality were analyzed using stepwise logistic regression.
Results
Twenty-eight patients with HIV-negative cryptococcal meningitis had seizures, including 13 with early seizures and 15 with late seizures. The mean time interval from HIV-negative cryptococcal meningitis to first seizure in the early and late seizure groups were 1.5 and 51.4 days, respectively. Nine out of the 28 cases (32%) occurred within 24 hours of presentation. The overall mortality rate was 54% (15/28) and two patients progressed to epilepsy.
Conclusions
Patients with seizure have worse outcomes and longer hospitalization. Most first seizures occur within one year after the diagnosis of HIV-negative cryptococcal meningitis.
doi:10.1186/s12883-014-0208-x
PMCID: PMC4203868  PMID: 25307800
Outcome; Risk factors; Seizures; HIV-negative cryptococcal meningitis
6.  Longitudinal Brain White Matter Alterations in Minimal Hepatic Encephalopathy before and after Liver Transplantation 
PLoS ONE  2014;9(8):e105887.
Cerebral edema is the common pathogenic mechanism for cognitive impairment in minimal hepatic encephalopathy. Whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved after liver transplantation remains an open question. To characterize white matter integrity before and after liver transplantation in patients with minimal hepatic encephalopathy, multiple diffusivity indices acquired via diffusion tensor imaging was applied. Twenty-eight patients and thirty age- and sex-matched healthy volunteers were included. Multiple diffusivity indices were obtained from diffusion tensor images, including mean diffusivity, fractional anisotropy, axial diffusivity and radial diffusivity. The assessment was repeated 6–12 month after transplantation. Differences in white matter integrity between groups, as well as longitudinal changes, were evaluated using tract-based spatial statistical analysis. Correlation analyses were performed to identify first scan before transplantation and interval changes among the neuropsychiatric tests, clinical laboratory tests, and diffusion tensor imaging indices. After transplantation, decreased water diffusivity without fractional anisotropy change indicating reversible cerebral edema was found in the left anterior cingulate, claustrum, postcentral gyrus, and right corpus callosum. However, a progressive decrease in fractional anisotropy and an increase in radial diffusivity suggesting demyelination were noted in temporal lobe. Improved pre-transplantation albumin levels and interval changes were associated with better recoveries of diffusion tensor imaging indices. Improvements in interval diffusion tensor imaging indices in the right postcentral gyrus were correlated with visuospatial function score correction. In conclusion, longitudinal voxel-wise analysis of multiple diffusion tensor imaging indices demonstrated different white matter changes in minimal hepatic encephalopathy patients. Transplantation improved extracellular cerebral edema and the results of associated cognition tests. However, white matter demyelination may advance in temporal lobe.
doi:10.1371/journal.pone.0105887
PMCID: PMC4148329  PMID: 25166619
7.  Diffusion Tensor Imaging Study of White Matter Damage in Chronic Meningitis 
PLoS ONE  2014;9(6):e98210.
Tuberculous meningitis (TBM) and cryptococcal meningitis (CM) are two of the most common types of chronic meningitis. This study aimed to assess whether chronic neuro-psychological sequelae are associated with micro-structure white matter (WM) damage in HIV-negative chronic meningitis. Nineteen HIV-negative TBM patients, 13 HIV-negative CM patients, and 32 sex- and age-matched healthy volunteers were evaluated and compared. The clinical relevance of WM integrity was studied using voxel-based diffusion tensor imaging (DTI) magnetic resonance imaging. All of the participants underwent complete medical and neurologic examinations, and neuro-psychological testing. Differences in DTI indices correlated with the presence of neuro-psychological rating scores and cerebrospinal fluid (CSF) analysis during the initial hospitalization. Patients with CM had more severe cognitive deficits than healthy subjects, especially in TBM. There were changes in WM integrity in several limbic regions, including the para-hippocampal gyrus and cingulate gyrus, and in the WM close to the globus pallidus. A decline in WM integrity close to the globus pallidus and anterior cingulate gyrus was associated with worse CSF analysis profiles. Poorer DTI parameters directly correlated with worse cognitive performance on follow-up. These correlations suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities. Abnormalities in the limbic system and globus pallidus, with their close relationship to the CSF space, may be specific biomarkers for disease evaluation.
doi:10.1371/journal.pone.0098210
PMCID: PMC4043527  PMID: 24892826
8.  The Roles of Biomarkers of Oxidative Stress and Antioxidant in Alzheimer's Disease: A Systematic Review 
BioMed Research International  2014;2014:182303.
Purpose. Oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). This paper aims to examine whether biomarkers of oxidative stress and antioxidants could be useful biomarkers in AD, which might form the bases of future clinical studies. Methods. PubMed, SCOPUS, and Web of Science were systematically queried to obtain studies with available data regarding markers of oxidative stress and antioxidants from subjects with AD. Results and Conclusion. Although most studies show elevated serum markers of lipid peroxidation in AD, there is no sufficient evidence to justify the routine use of biomarkers as predictors of severity or outcome in AD.
doi:10.1155/2014/182303
PMCID: PMC4053273  PMID: 24949424
9.  Association between Oxidative Stress and Outcome in Different Subtypes of Acute Ischemic Stroke 
BioMed Research International  2014;2014:256879.
Objectives. This study investigated serum thiobarbituric acid-reactive substances (TBARS) and free thiol levels in different subtypes of acute ischemic stroke (AIS) and evaluated their association with clinical outcomes. Methods. This prospective study evaluated 100 AIS patients, including 75 with small-vessel and 25 with large-vessel diseases. Serum oxidative stress (TBARS) and antioxidant (thiol) were determined within 48 hours and days 7 and 30 after stroke. For comparison, 80 age- and sex-matched participants were evaluated as controls. Results. Serum TBARS was significantly higher and free thiol was lower in stroke patients than in the controls on days 1 and 7 after AIS. The level of free thiol was significantly lower in the large-vessel disease than in the small-vessel disease on day 7 after stroke. Using the stepwise logistic regression model for potential variables, only stroke subtype, NIHSS score, and serum TBARS level were independently associated with three-month outcome. Higher TBARS and lower thiol levels in the acute phase of stroke were associated with poor outcome. Conclusions. Patients with large-vessel disease have higher oxidative stress but lower antioxidant defense compared to those with small-vessel disease after AIS. Serum TBARS level at the acute phase of stroke is a potential predictor for three-month outcome.
doi:10.1155/2014/256879
PMCID: PMC4034452  PMID: 24895559
10.  Elevated Serum Vascular Cell Adhesion Molecule-1 Is Associated with Septic Encephalopathy in Adult Community-Onset Severe Sepsis Patients 
BioMed Research International  2014;2014:598762.
Background and Aim. Septic encephalopathy (SE) is a common complication of severe sepsis. Increased concentrations of circulating soluble adhesion molecules are reported in septic patients. This study aimed to determine whether serum adhesion molecules are associated with SE. Methods. Seventy nontraumatic, nonsurgical adult patients with severe sepsis admitted through ER were evaluated. Serum adhesion molecules were assessed for their relationship with SE, and compared with other clinical predictors and biomarkers. Results. Twenty-three (32.8%) patients had SE. SE group had higher in-hospital mortality (40% versus 11%, P = 0.009) and their sVCAM-1, sICAM-1, and lactate levels on admission were also higher than non-SE group. By stepwise logistic regression model, sVCAM-1, age, and maximum 24-hours SOFA score were independently associated with septic encephalopathy. The AUC analysis of ROC curve of different biomarkers showed that sVCAM-1 is better to predict SE. The sVCAM-1 levels in the SE group were significantly higher than those of the non-SE group at three time periods (Days 1, 4, and 7). Conclusions. Septic encephalopathy implies higher mortality in nontraumatic, nonsurgical patients with severe sepsis. VCAM-1 level on presentation is a more powerful predictor of SE in these patients than lactate concentration and other adhesion molecules on admission.
doi:10.1155/2014/598762
PMCID: PMC4032707  PMID: 24883317
11.  The Association among Antioxidant Enzymes, Autoantibodies, and Disease Severity Score in Systemic Lupus Erythematosus: Comparison of Neuropsychiatric and Nonneuropsychiatric Groups 
BioMed Research International  2014;2014:137231.
Background. Antioxidative capacity plays an important role in the severity of systemic lupus erythematosus (SLE), which is characterized by autoantibodies. This study aimed to determine the relationship among autoantibody titers, antioxidative stress reserve, and severity of SLE. Methods. The autoantibody titers, clinical markers, antioxidant enzyme levels, and disease activity index (SLEDAI-2k) of 32 SLE patients and 16 healthy controls were compared. We also compared both the neuropsychiatric (NPSLE) and nonneuropsychiatric (non-NPSLE) groups. Results. Superoxide dismutase in red blood cells was significantly lower in the SLE than in the control group. CRP levels are significant higher in SLE patients than in control group (P = 0.034). Among the autoantibodies, anti-U1RNP (P = 0.008), a-Sm (P = 0.027), and anti-ribosomal p (P = 0.028) significantly negatively correlated with glutathione levels. There has no significant correlation between SLE disease activity indexes (SLEDAI) and levels of C3, C4, and antioxidant enzymes. Conclusions. Erythrocyte superoxide dismutase is significantly lower in both NPSLE and non-NPSLE groups. SLE patients have both higher CRP and autoantibodies level and decreased superoxide dismutase level than the healthy control group.
doi:10.1155/2014/137231
PMCID: PMC4024413  PMID: 24877055
12.  The Association between Autoantibodies and Peripheral Neuropathy in Lupus Nephritis 
BioMed Research International  2014;2014:524940.
Background and Aim. The sensitivity and specificity of biomarkers used for predicting peripheral neuropathy in patients with systemic lupus erythematosus (SLE) and nephritis (SLE-LN) remain unsatisfactory. This study aimed to determine the autoantibodies levels in SLE-LN patients with peripheral neuropathy. Methods. Data of 559 SLE-LN patients were collected retrospectively, including titers of autoantibodies, electrodiagnostic studies, and clinical manifestations. Results. The neurologic manifestations of the SLE-LN patients were diverse and nonspecific. The prevalence rate of peripheral polyneuropathy was 2.68%, of which about 73.33% was mixed sensory-motor polyneuropathy. Numbness and functional gastrointestinal problems were the most prevalent symptoms and these were noted in every subtype of peripheral neuropathy. Among all the serology markers, anti-Ro was significantly associated with neuropathy related to SLE (P = 0.009). Conclusion. Peripheral neuropathy among LN patients is rare and may be easily overlooked. This study demonstrated that positive anti-Ro antibody may imply neuropathy in LN patients. Thus, anti-Ro can be considered a biomarker that should be added to the panel of conventional autoantibodies in LN patients.
doi:10.1155/2014/524940
PMCID: PMC4017733  PMID: 24864250
13.  Effects of Metformin on the Cerebral Metabolic Changes in Type 2 Diabetic Patients 
The Scientific World Journal  2014;2014:694326.
Metformin, a widely used antidiabetic drug, has numerous effects on human metabolism. Based on emerging cellular, animal, and epidemiological studies, we hypothesized that metformin leads to cerebral metabolic changes in diabetic patients. To explore metabolism-influenced foci of brain, we used 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography for type 2 diabetic patients taking metformin (MET, n = 18), withdrawing from metformin (wdMET, n = 13), and not taking metformin (noMET, n = 9). Compared with the noMET group, statistical parametric mapping showed that the MET group had clusters with significantly higher metabolism in right temporal, right frontal, and left occipital lobe white matter and lower metabolism in the left parahippocampal gyrus, left fusiform gyrus, and ventromedial prefrontal cortex. In volume of interest (VOI-) based group comparisons, the normalized FDG uptake values of both hypermetabolic and hypometabolic clusters were significantly different between groups. The VOI-based correlation analysis across the MET and wdMET groups showed a significant negative correlation between normalized FDG uptake values of hypermetabolic clusters and metformin withdrawal durations and a positive but nonsignificant correlation in the turn of hypometabolic clusters. Conclusively, metformin affects cerebral metabolism in some white matter and semantic memory related sites in patients with type 2 diabetes.
doi:10.1155/2014/694326
PMCID: PMC3982461  PMID: 24782665
14.  Statin therapy reduces oxidized low density lipoprotein level, a risk factor for stroke outcome 
Critical Care  2014;18(1):R16.
Introduction
Statins are reported to have anti-inflammatory and anti-oxidative effects aside from cholesterol-lowering effects. This study aimed to evaluate the effects of statin therapy on oxidized LDL (Ox-LDL) and the clinical outcome of patients with acute ischemic stroke (AIS).
Methods
This prospective study enrolled 120 patients with AIS divided in the statin (n = 55) and non-statin (n = 65) groups. Eighty sex- and age- matched participants were recruited as risk controls. Ox-LDL was measured using a monoclonal antibody-based enzyme-linked immune-sorbent assay at different time points after AIS. The clinical outcomes were analyzed between the statin and non-statin groups.
Results
Plasma Ox-LDL was significantly higher in stroke patients than in the controls (P < 0.001). Plasma Ox-LDL level was significantly reduced in the statin group on day 7 and day 30 compared to the non-statin group (P < 0.01). The plasma Ox-LDL positively correlated with serum total cholesterol, LDL-cholesterol, and hemoglobin A1c (HbA1c). Among the potential risk factors, only National Institutes of Health stroke scale (NIHSS) score and Ox-LDL level on admission were independently associated with 3-month outcome.
Conclusions
Our study demonstrates that statin therapy reduces plasma Ox-LDL level after AIS. Plasma Ox-LDL may be a more powerful predictor than serum LDL, high-sensitivity C-reactive protein or white blood cell counts for stroke outcome. Therefore, assay of plasma Ox-LDL should be added as a predictor among the panel of conventional biomarkers in stroke outcome.
doi:10.1186/cc13695
PMCID: PMC4056016  PMID: 24423248
15.  Long-term effects on carotid intima-media thickness after radiotherapy in patients with nasopharyngeal carcinoma 
Background
Vascular abnormalities are the predominant histologic changes associated with radiation in nasopharyngeal carcinoma (NPC). This study examined if the duration after radiotherapy correlates with the progression of carotid intima-media thickness (IMT) and investigated its relationship with inflammatory markers.
Methods
One hundred and five NPC patients post-radiotherapy for more than one year and 25 healthy control subjects were examined by B-mode ultrasound for IMT measurement at the far wall of the common carotid artery (CCA). Surrogate markers including lipid profile, HbA1c, and high sensitive C-reactive protein (hs-CRP) were assessed.
Results
The IMT of CCA was significantly increased in NPC patients and carotid plaque was detected in 38 NPC patients (38/105, 36.2%). Significant risk factors for carotid plaques included age, duration after radiotherapy, and HbA1c levels. Age, duration after radiotherapy, hs-CRP, HbA1c, and platelet count positively correlated with IMT. The cut-off value of age and duration after radiotherapy for the presence of plaque was 52.5 years and 42.5 months, respectively. In NPC subjects, multiple linear regression analysis revealed that age, gender, duration after radiotherapy and platelet counts were independently associated with CCA IMT. After adjustments for age, gender and platelet counts, IMT increased in a linear manner with duration after radiotherapy.
Conclusions
Radiation-induced vasculopathy is a dynamic and progressive process due to late radiation effects. Extra-cranial color-coded duplex sonography can be part of routine follow-up in NPC patients aged ≥50 years at 40 months post-radiotherapy.
doi:10.1186/1748-717X-8-261
PMCID: PMC3827874  PMID: 24196030
Atherosclerosis; Nasopharyngeal carcinoma; Radiotherapy; Risk factors
16.  The association among leukocyte apoptosis, autoantibodies and disease severity in systemic lupus erythematosus 
Background
Both apoptosis and autoantibodies are important factors associated with disease activity in the pathogenesis of systemic lupus erythematosus (SLE). This study tested the hypothesis that increased leukocyte apoptosis is associated with elevated levels of autoantibodies and the disease activity of SLE.
Methods
Leukocyte apoptosis was determined by flow cytometry, including annexin V, APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 23 patients with SLE. Leukocyte apoptosis was also evaluated in nine patients with Sjogren’s syndrome (SJS) and in 20 volunteer subjects. Titers of common autoantibodies and the disease activity index (SLEDAI-2 k) of the SLE patients were also determined.
Results
Except for annexin V and APO 2.7 of monocytes and late apoptosis (annexin V + 7-ADD) of lymphocytes, apoptosis in the total and in subsets of leukocytes were significantly higher in SLE patients than in controls (all p < 0.05, post hoc analysis). The mean percentage of late apoptosis of leukocytes (annexin V + 7-AAD) positively correlated with levels of anti-Ro52/60 (r = 0.513, p < 0.01), anti-La (r = 0.439, p = 0.04), and anti-Mi-2 (r = 0.492, p = 0.02), and inversely correlated with both C3 and C4 levels, although not statistically significant. The percentage of APO2.7 of CD19+ cells positively correlated with SLEDAI-2 K score (p = 0.01).
Conclusions
Leukocyte apoptosis is significantly higher in patients with SLE and correlates well with the levels of several autoantibodies. The APO2.7 of B-lymphocyte (CD19+) cells positively correlates with the disease activity of SLE.
doi:10.1186/1479-5876-11-261
PMCID: PMC3853096  PMID: 24138706
Autoantibodies; Diseases severity score; Leukocyte apoptosis; Systemic lupus erythematosus
17.  Structural and cognitive deficits in chronic carbon monoxide intoxication: a voxel-based morphometry study 
BMC Neurology  2013;13:129.
Background
Patients with carbon monoxide (CO) intoxication may develop ongoing neurological and psychiatric symptoms that ebb and flow, a condition often called delayed encephalopathy (DE). The association between morphologic changes in the brain and neuropsychological deficits in DE is poorly understood.
Methods
Magnetic resonance imaging and neuropsychological tests were conducted on 11 CO patients with DE, 11 patients without DE, and 15 age-, sex-, and education-matched healthy subjects. Differences in gray matter volume (GMV) between the subgroups were assessed and further correlated with diminished cognitive functioning.
Results
As a group, the patients had lower regional GMV compared to controls in the following regions: basal ganglia, left claustrum, right amygdala, left hippocampus, parietal lobes, and left frontal lobe. The reduced GMV in the bilateral basal ganglia, left post-central gyrus, and left hippocampus correlated with decreased perceptual organization and processing speed function. Those CO patients characterized by DE patients had a lower GMV in the left anterior cingulate and right amygdala, as well as lower levels of cognitive function, than the non-DE patients.
Conclusions
Patients with CO intoxication in the chronic stage showed a worse cognitive and morphologic outcome, especially those with DE. This study provides additional evidence of gray matter structural abnormalities in the pathophysiology of DE in chronic CO intoxicated patients.
doi:10.1186/1471-2377-13-129
PMCID: PMC3850907  PMID: 24083408
Carbon monoxide intoxication; Cognitive deficits; Delayed encephalopathy; Magnetic resonance imaging; Voxel-based morphometry
18.  The diagnostic value of ultrasonography in carpal tunnel syndrome: a comparison between diabetic and non-diabetic patients 
BMC Neurology  2013;13:65.
Background
To compare the value of ultrasonography for diagnosing carpal tunnel syndrome (CTS) in patients with and without diabetes mellitus (DM).
Methods
Eighty non-DM and 40 DM patients with electromyography-confirmed CTS were assessed and underwent high-resolution ultrasonography of the wrists. Cross-sectional area (CSA) and flattening ratio (FR) of the median nerve were measured at the carpal tunnel outlet (D) and wrist crease (W).
Results
The 80 non-DM and 40 DM patients had 81 and 59 CTS-hands, respectively. The CSA_D and CSA_W were significantly larger in the CTS-hands and DM-CTS-hands compared to the normal control (p < 0.001). However, there is no difference of CSA_D and CSA_W between DM and non-DM CTS patients. Receiver operating characteristics [ROC] curve analysis revealed that CSA_W ≥13 mm2 was the most powerful predictor of CTS in DM (area under curve [AUC] = 0.72; sensitivity 72.9%, specificity 61.9%) and non-DM (AUC = 0.72; sensitivity 78.5%, specificity 53.2%) patients. The CSA positively correlated with the distal motor latency of the median compound motor action potential (CMAP), distal sensory latency of the median sensory nerve action potential (SNAP), and latency of the median F wave, but negatively correlated with the amplitude of the median CMAP, amplitude of the median SNAP, and sensory NCV of the median nerve. Stepwise logistic regression revealed that CSA_W (OR 1.21, 95% CI 1.07-1.38; p = 0.003) was independently associated with CTS in DM patients and any 1 mm2 increase in CSA_W increased the rate of CTS by 28%.
Conclusions
The CSA of the median nerve at the outlet and wrist crease are significantly larger in CTS hands in both DM and non-DM patients compared to normal hands. The CSA of the median nerve by ultrasonography may be a diagnostic tool for evaluating CTS in DM and non-DM patients.
doi:10.1186/1471-2377-13-65
PMCID: PMC3697998  PMID: 23800072
Carpal tunnel syndrome; Cross-sectional area; Median nerve; Ultrasonography
19.  Bacterial brain abscess in patients with nasopharyngeal carcinoma following radiotherapy: microbiology, clinical features and therapeutic outcomes 
BMC Infectious Diseases  2012;12:204.
Background
This study aimed to analyze the clinical features, causative pathogens, neuro-imaging findings, and therapeutic outcomes of bacterial brain abscess in patients with nasopharyngeal carcinoma (NPC) following radiotherapy.
Methods
NPC patients with bacterial brain abscess were evaluated. Their clinical data were collected over a 22-year period. For comparison, the clinical features, causative pathogens, neuro-imaging findings, and therapeutic outcomes between NPC and non-NPC patients were analyzed.
Results
NPC accounted for 5.7% (12/210) of the predisposing factors, with Viridans streptococci and Staphylococcus aureus as the two most common causative pathogens. Significant statistical analysis between the two groups (NPC and non-NPC patients) included chronic otitis media (COM) as the underlying disease, post-radiation necrosis by neuro-imaging, and the temporal lobe as the most common site of brain abscesses. The fatality rate in patients with and without NPC was 16.7% and 20.7%, respectively.
Conclusions
NPC patients with bacterial brain abscess frequently have COM as the underlying disease. Neuro-imaging often reveals both post-radiation necrosis and the temporal lobe as the most common site of brain abscesses, the diagnosis of which is not always a straightforward process. Radiation necrosis can mimic brain abscess on neuro-imaging and pose significant diagnostic challenges. Early diagnosis and treatment is essential for survival.
doi:10.1186/1471-2334-12-204
PMCID: PMC3482557  PMID: 22943134
Bacterial brain abscess; Nasopharyngeal carcinoma; Therapeutic outcome
20.  Is there a role of whole-body bone scan in patients with esophageal squamous cell carcinoma 
BMC Cancer  2012;12:328.
Background
Correct detection of bone metastases in patients with esophageal squamous cell carcinoma is pivotal for prognosis and selection of an appropriate treatment regimen. Whole-body bone scan for staging is not routinely recommended in patients with esophageal squamous cell carcinoma. The aim of this study was to investigate the role of bone scan in detecting bone metastases in patients with esophageal squamous cell carcinoma.
Methods
We retrospectively evaluated the radiographic and scintigraphic images of 360 esophageal squamous cell carcinoma patients between 1999 and 2008. Of these 360 patients, 288 patients received bone scan during pretreatment staging, and sensitivity, specificity, positive predictive value, and negative predictive value of bone scan were determined. Of these 360 patients, surgery was performed in 161 patients including 119 patients with preoperative bone scan and 42 patients without preoperative bone scan. Among these 161 patients receiving surgery, 133 patients had stages II + III disease, including 99 patients with preoperative bone scan and 34 patients without preoperative bone scan. Bone recurrence-free survival and overall survival were compared in all 161 patients and 133 stages II + III patients, respectively.
Results
The diagnostic performance for bone metastasis was as follows: sensitivity, 80%; specificity, 90.1%; positive predictive value, 43.5%; and negative predictive value, 97.9%. In all 161 patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0.009, univariately). In multivariate comparison, absence of preoperative bone scan (P = 0.012, odds ratio: 5.053) represented the independent adverse prognosticator for bone recurrence-free survival. In 133 stages II + III patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0.003, univariately) and overall survival (P = 0.037, univariately). In multivariate comparison, absence of preoperative bone scan was independently associated with inferior bone recurrence-free survival (P = 0.009, odds ratio: 5.832) and overall survival (P = 0.029, odds ratio: 1.603).
Conclusions
Absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival, suggesting that whole-body bone scan should be performed before esophagectomy in patients with esophageal squamous cell carcinoma, especially in patients with advanced stages.
doi:10.1186/1471-2407-12-328
PMCID: PMC3443043  PMID: 22853826
Radionuclide imaging; Esophageal cancer; Squamous cell carcinoma; Metastasis; Esophagectomy
21.  Predictors and outcomes of shunt-dependent hydrocephalus in patients with aneurysmal sub-arachnoid hemorrhage 
BMC Surgery  2012;12:12.
Background
Hydrocephalus following spontaneous aneurysmal sub-arachnoid hemorrhage (SAH) is often associated with unfavorable outcome. This study aimed to determine the potential risk factors and outcomes of shunt-dependent hydrocephalus in aneurysmal SAH patients but without hydrocephalus upon arrival at the hospital.
Methods
One hundred and sixty-eight aneurysmal SAH patients were evaluated. Using functional scores, those without hydrocephalus upon arrival at the hospital were compared to those already with hydrocephalus on admission, those who developed it during hospitalization, and those who did not develop it throughout their hospital stay. The Glasgow Coma Score, modified Fisher SAH grade, and World Federation of Neurosurgical Societies grade were determined at the emergency room. Therapeutic outcomes immediately after discharge and 18 months after were assessed using the Glasgow Outcome Score.
Results
Hydrocephalus accounted for 61.9% (104/168) of all episodes, including 82 with initial hydrocephalus on admission and 22 with subsequent hydrocephalus. Both the presence of intra-ventricular hemorrhage on admission and post-operative intra-cerebral hemorrhage were independently associated with shunt-dependent hydrocephalus in patients without hydrocephalus on admission. After a minimum 1.5 years of follow-up, the mean Glasgow outcome score was 3.33 ± 1.40 for patients with shunt-dependent hydrocephalus and 4.21 ± 1.19 for those without.
Conclusions
The presence of intra-ventricular hemorrhage, lower mean Glasgow Coma Scale score, and higher mean scores of the modified Fisher SAH and World Federation of Neurosurgical grading on admission imply risk of shunt-dependent hydrocephalus in patients without initial hydrocephalus. These patients have worse short- and long-term outcomes and longer hospitalization.
doi:10.1186/1471-2482-12-12
PMCID: PMC3467164  PMID: 22765765
Outcome; Risk factors; Hydrocephalus after spontaneous aneurysmal subarachnoid hemorrhage
22.  Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room 
Background and aim
The sensitivity and specificity of biomarkers and scoring systems used for predicting fatality of severe sepsis patients remain unsatisfactory. This study aimed to determine the prognostic value of circulating plasma DNA levels in severe septic patients presenting at the Emergency Department (ED).
Methods
Sixty-seven consecutive patients with severe sepsis and 33 controls were evaluated. Plasma DNA levels were estimated by real-time quantitative polymerase chain reaction assay using primers for the human β-hemoglobin and ND2 gene. The patients’ clinical and laboratory data on admission were analyzed.
Results
The median plasma nuclear and mitochondria DNA levels for severe septic patients on admission were significantly higher than those of the controls. The mean plasma nuclear DNA level on admission correlated with lactate concentration (γ = 0.36, p = 0.003) and plasma mitochondrial DNA on admission (γ = 0.708, p < 0.001). Significant prognostic factors for fatality included mechanical ventilation within the first 24 hours (p = 0.013), mean sequential organ failure assessment (SOFA) score on admission (p = 0.04), serum lactate (p < 0.001), and both plasma nuclear and mitochondrial DNA on admission (p < 0.001). Plasma mitochondrial DNA was an independent predictor of fatality by stepwise logistic regression such that an increase by one ng/mL in level would increase fatality rate by 0.7%.
Conclusion
Plasma DNA has potential use for predicting outcome in septic patients arriving at the emergency room. Plasma mitochondrial DNA level on admission is a more powerful predictor than lactate concentration or SOFA scores on admission.
doi:10.1186/1479-5876-10-130
PMCID: PMC3441240  PMID: 22720733
Hospital mortality; Mitochondrial DNA; Nucleus DNA; Severe sepsis
23.  Connectivity of Default-Mode Network Is Associated with Cerebral Edema in Hepatic Encephalopathy 
PLoS ONE  2012;7(5):e36986.
Cerebral edema, a well-known feature of acute liver disease, can occur in cirrhotic patients regardless of hepatic encephalopathy (HE) and adversely affect prognosis. This study characterized and correlated functional HE abnormalities in the brain to cerebral edema using resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). Forty-one cirrhotic patients (16 without HE, 14 minimal HE, 11 overt HE) and 32 healthy controls were assessed. The HE grade in cirrhotic patients was evaluated by the West Haven criteria and neuro-psychological examinations. Functional connectivity correlation coefficient (fc-CC) of the default mode network (DMN) was determined by rs-fMRI, while the corresponding mean diffusivity (MD) was obtained from DTI. Correlations among inter-cortical fc-CC, DTI indices, Cognitive Ability Screening Instrument scores, and laboratory tests were also analyzed. Results showed that gradual reductions of HE-related consciousness levels, from “without HE” or “minimal HE” to “overt HE”, correlated with decreased anterior-posterior fc-CC in DMN [F(4.415), p = 0.000)]. The MD values from regions with anterior-posterior fc-CC differences in DMN revealed significant differences between the overt HE group and other groups. Increased MD in this network was inversely associated with decreased fc-CC in DMN and linearly correlated with poor cognitive performance. In conclusion, cerebral edema can be linked to altered cerebral temporal architecture that modifies both within- and between-network connectivity in HE. Reduced fc-CC in DMN is associated with behavior and consciousness deterioration. Through appropriate targets, rs-fMRI technology may provide relevant supplemental information for monitoring HE and serve as a new biomarker for clinical diagnosis.
doi:10.1371/journal.pone.0036986
PMCID: PMC3356373  PMID: 22623966
24.  Impaired Small-World Network Efficiency and Dynamic Functional Distribution in Patients with Cirrhosis 
PLoS ONE  2012;7(5):e35266.
Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome and a major complication of liver cirrhosis. Dysmetabolism of the brain, related to elevated ammonia levels, interferes with intercortical connectivity and cognitive function. For evaluation of network efficiency, a ‘small-world’ network model can quantify the effectiveness of information transfer within brain networks. This study aimed to use small-world topology to investigate abnormalities of neuronal connectivity among widely distributed brain regions in patients with liver cirrhosis using resting-state functional magnetic resonance imaging (rs-fMRI). Seventeen cirrhotic patients without HE, 9 with minimal HE, 9 with overt HE, and 35 healthy controls were compared. The interregional correlation matrix was obtained by averaging the rs-fMRI time series over all voxels in each of the 90 regions using the automated anatomical labeling model. Cost and correlation threshold values were then applied to construct the functional brain network. The absolute and relative network efficiencies were calculated; quantifying distinct aspects of the local and global topological network organization. Correlations between network topology parameters, ammonia levels, and the severity of HE were determined using linear regression and ANOVA. The local and global topological efficiencies of the functional connectivity network were significantly disrupted in HE patients; showing abnormal small-world properties. Alterations in regional characteristics, including nodal efficiency and nodal strength, occurred predominantly in the association, primary, and limbic/paralimbic regions. The degree of network organization disruption depended on the severity of HE. Ammonia levels were also significantly associated with the alterations in local network properties. Results indicated that alterations in the rs-fMRI network topology of the brain were associated with HE grade; and that focal or diffuse lesions disturbed the functional network to further alter the global topology and efficiency of the whole brain network. These findings provide insights into the functional changes in the human brain in HE.
doi:10.1371/journal.pone.0035266
PMCID: PMC3341390  PMID: 22563460
25.  White Matter Abnormalities Correlating with Memory and Depression in Heroin Users under Methadone Maintenance Treatment 
PLoS ONE  2012;7(4):e33809.
Methadone maintenance treatment (MMT) has elevated rates of co-morbid memory deficit and depression that are associated with higher relapse rates for substance abuse. White matter (WM) disruption in MMT patients have been reported but their impact on these co-morbidities is unknown. This study aimed to investigate changes in WM integrity of MMT subjects using diffusion tensor image (DTI), and their relationship with history of heroin and methadone use in treated opiate-dependent individuals. The association between WM integrity changes from direct group comparisons and the severity of memory deficit and depression was also investigated. Differences in WM integrity between 35 MMT patients and 23 healthy controls were evaluated using DTI with tract-based spatial statistical analysis. Differences in DTI indices correlated with diminished memory function, Beck Depression Inventory, duration of heroin use and MMT, and dose of heroin and methadone administration. Changes in WM integrity were found in several WM regions, including the temporal and frontal lobes, pons, cerebellum, and cingulum bundles. The duration of MMT was associated with declining DTI indices in the superior longitudinal fasciculus and para-hippocampus. MMT patients had more memory and emotional deficits than healthy subjects. Worse scores in both depression and memory functions were associated with altered WM integrity in the superior longitudinal fasciculus, para-hippocampus, and middle cerebellar peduncle in MMT. Patients on MMT also had significant WM differences in the reward circuit and in depression- and memory-associated regions. Correlations among decreased DTI indices, disease severity, and accumulation effects of methadone suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities in MMT.
doi:10.1371/journal.pone.0033809
PMCID: PMC3322116  PMID: 22496768

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